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Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis

  • Authors:
    • Jing Zhao
    • Mingming Ma
    • Lei Li
    • Gaoli Fang
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 44
    |
    Published online on: January 4, 2023
       https://doi.org/10.3892/mmr.2023.12931
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Abstract

Oxysophoridine (OSR) is an alkaloid extracted from Sophora alopecuroides L. and exerts beneficial effects in cerebral ischemia/reperfusion (I/R) injury. However, the molecular mechanism underlying the regulatory effects of OSR in cerebral I/R injury remains unclear. In the present study, a cerebral I/R injury rat model was established by occlusion of the right middle cerebral artery. Hematoxylin and eosin and triphenyltetrazolium chloride staining were performed to assess histopathological changes and the extent of cerebral injury to the brain. A Cell Counting Kit‑8 and TUNEL assay and western blotting were performed to assess cell viability and apoptosis. Ferroptosis and oxidative stress were evaluated based on ATP and Fe2+ levels and DCFH‑DA staining. The protein expression levels of inflammatory factors were assessed using ELISA. The protein expression levels of members of the toll‑like receptor (TLR)4/p38MAPK signaling pathway were evaluated using immunofluorescence staining and western blotting. The results demonstrated that OSR decreased brain injury and neuronal apoptosis in the hippocampus in I/R‑induced rats. OSR inhibited reactive oxygen species (ROS) production, decreased levels of ATP, Fe2+ and acyl‑CoA synthetase long‑chain family member 4 (ACSL4) and transferrin 1 protein and increased the protein expression levels of ferritin 1 and glutathione peroxidase 4. Furthermore, OSR blocked TLR4/p38MAPK signaling in brain tissue in the I/R‑induced rat. In vitro experiments demonstrated that TLR4 overexpression induced generation of ROS, ATP and Fe2+, which promoted the expression of ferroptosis‑associated proteins in hippocampal HT22 neuronal cells. The ferroptosis inducer erastin decreased the effects of OSR on oxygen‑glucose deprivation/reoxygenation (OGD/R)‑induced cell viability, oxidative stress and inflammatory response. Together, the results demonstrated that OSR alleviated cerebral I/R injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis.
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1 

Liu W, Wong A, Law AC and Mok VC: Cerebrovascular disease, amyloid plaques, and dementia. Stroke. 46:1402–1407. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Lanzino G and Brown RD Jr: Introduction: Management of ischemic cerebrovascular disease. Neurosurg Focus. 36:1–2. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Wang L, Jia J, Hong Z, Zhang L and Zhang J: Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease. Lipids Health Dis. 20:1082021. View Article : Google Scholar : PubMed/NCBI

4 

Lu J and Wang DM: Update in endovascular therapy of ischemic cerebrovascular disease. Zhonghua Wai Ke Za Zhi. 59:192–195. 2021.(In Chinese). PubMed/NCBI

5 

Lim S, Kim TJ, Kim YJ, Kim C, Ko SB and Kim BS: Senolytic Therapy for cerebral ischemia-reperfusion injury. Int J Mol Sci. 22:119672021. View Article : Google Scholar : PubMed/NCBI

6 

Yang Z, Weian C, Susu H and Hanmin W: Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms. Eur J Pharmacol. 771:145–151. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Banz Y and Rieben R: Role of complement and perspectives for intervention in ischemia-reperfusion damage. Ann Med. 44:205–217. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Al-Mufti F, Amuluru K, Roth W, Nuoman R, El-Ghanem M and Meyers PM: Cerebral ischemic reperfusion injury following recanalization of large vessel occlusions. Neurosurgery. 82:781–789. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Yao XQ, Zhang YH, Long W and Liu PX: Oxysophoridine suppresses the growth of hepatocellular carcinoma in mice: In vivo and cDNA microarray studies. Chin J Integr Med. 18:209–213. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Wang R, Deng X, Gao Q, Wu X, Han L, Gao X, Zhao S, Chen W, Zhou R, Li Z and Bai C: Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review. J Ethnopharmacol. 248:1121722020. View Article : Google Scholar : PubMed/NCBI

11 

Meng C, Liu C, Liu Y and Wu F: Oxysophoridine attenuates the injury caused by acute myocardial infarction in rats through anti-oxidative, anti-inflammatory and anti-apoptotic pathways. Mol Med Rep. 11:527–532. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Cao Z, Chen L, Liu Y and Peng T: Oxysophoridine rescues spinal cord injury via anti-inflammatory, anti-oxidative stress and anti-apoptosis effects. Mol Med Rep. 17:2523–2528. 2018.PubMed/NCBI

13 

Wang H, Li Y, Jiang N, Chen X, Zhang Y, Zhang K, Wang T, Hao Y, Ma L, Zhao C, et al: Protective effect of oxysophoridine on cerebral ischemia/reperfusion injury in mice. Neural Regen Res. 8:1349–1359. 2013.PubMed/NCBI

14 

Zhai Z and Feng J: Left-right asymmetry influenced the infarct volume and neurological dysfunction following focal middle cerebral artery occlusion in rats. Brain Behav. 8:e011662018. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Mehanna R and Jankovic J: Movement disorders in cerebrovascular disease. Lancet Neurol. 12:597–608. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Sveinsson OA, Kjartansson O and Valdimarsson EM: Cerebral ischemia/infarction-epidemiology, causes and symptoms. Laeknabladid. 100:271–279. 2014.(In Icelandic). PubMed/NCBI

18 

Suzuki H, Kanamaru H, Kawakita F, Asada R, Fujimoto M and Shiba M: Cerebrovascular pathophysiology of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Histol Histopathol. 36:143–158. 2021.PubMed/NCBI

19 

Qin Y, Zhang Q and Liu Y: Analysis of knowledge bases and research focuses of cerebral ischemia-reperfusion from the perspective of mapping knowledge domain. Brain Res Bull. 156:15–24. 2020. View Article : Google Scholar : PubMed/NCBI

20 

Kawadkar M, Mandloi AS, Saxena V, Tamadaddi C, Sahi C and Dhote VV: Noscapine alleviates cerebral damage in ischemia-reperfusion injury in rats. Naunyn Schmiedebergs Arch Pharmacol. 394:669–683. 2021. View Article : Google Scholar : PubMed/NCBI

21 

Guan X, Li Z, Zhu S, Cheng M, Ju Y, Ren L, Yang G and Min D: Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils. Life Sci. 264:1186602021. View Article : Google Scholar : PubMed/NCBI

22 

Wang G, Wang T, Zhang Y, Li F, Yu B and Kou J: Schizandrin protects against OGD/R-induced neuronal injury by suppressing autophagy: Involvement of the AMPK/mTOR pathway. Molecules. 24:36242019. View Article : Google Scholar : PubMed/NCBI

23 

Chen R, Wang Z, Zhi Z, Tian J, Zhao Y and Sun J: Targeting the TLR4/NF-κB pathway in β-amyloid-stimulated microglial cells: A possible mechanism that oxysophoridine exerts anti-oxidative and anti-inflammatory effects in an in vitro model of Alzheimer's disease. Brain Res Bull. 175:150–157. 2021. View Article : Google Scholar : PubMed/NCBI

24 

Rui C, Yuxiang L, Ning J, Ningtian M, Qingluan Z, Yinju H, Ru Z, Lin M, Tao S and Jianqiang Y: Anti-apoptotic and neuroprotective effects of oxysophoridine on cerebral ischemia both in vivo and in vitro. Planta Med. 79:916–923. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Wang TF, Lei Z, Li YX, Wang YS, Wang J, Wang SJ, Hao YJ, Zhou R, Jin SJ, Du J, et al: Oxysophoridine protects against focal cerebral ischemic injury by inhibiting oxidative stress and apoptosis in mice. Neurochem Res. 38:2408–2417. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Iadecola C and Anrather J: The immunology of stroke: From mechanisms to translation. Nat Med. 17:796–808. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Liu J, Chen Q, Jian Z, Xiong X, Shao L, Jin T, Zhu X and Wang L: Daphnetin protects against cerebral ischemia/reperfusion injury in mice via inhibition of TLR4/NF-κB signaling pathway. Biomed Res Int. 2016:28160562016. View Article : Google Scholar : PubMed/NCBI

28 

Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA and Lizasoain I: Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation. 115:1599–1608. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Zhu K, Zhu X, Sun S, Yang W, Liu S, Tang Z, Zhang R, Li J, Shen T and Hei M: Inhibition of TLR4 prevents hippocampal hypoxic-ischemic injury by regulating ferroptosis in neonatal rats. Exp Neurol. 345:1138282021. View Article : Google Scholar : PubMed/NCBI

30 

Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, et al: Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 171:273–285. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Guan X, Li X, Yang X, Yan J, Shi P, Ba L, Cao Y and Wang P: The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation. Life Sci. 235:1167952019. View Article : Google Scholar : PubMed/NCBI

32 

Guo H, Zhu L, Tang P, Chen D, Li Y, Li J and Bao C: Carthamin yellow improves cerebral ischemia-reperfusion injury by attenuating inflammation and ferroptosis in rats. Int J Mol Med. 47:522021. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhao J, Ma M, Li L and Fang G: Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis. Mol Med Rep 27: 44, 2023.
APA
Zhao, J., Ma, M., Li, L., & Fang, G. (2023). Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis. Molecular Medicine Reports, 27, 44. https://doi.org/10.3892/mmr.2023.12931
MLA
Zhao, J., Ma, M., Li, L., Fang, G."Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis". Molecular Medicine Reports 27.2 (2023): 44.
Chicago
Zhao, J., Ma, M., Li, L., Fang, G."Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis". Molecular Medicine Reports 27, no. 2 (2023): 44. https://doi.org/10.3892/mmr.2023.12931
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao J, Ma M, Li L and Fang G: Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis. Mol Med Rep 27: 44, 2023.
APA
Zhao, J., Ma, M., Li, L., & Fang, G. (2023). Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis. Molecular Medicine Reports, 27, 44. https://doi.org/10.3892/mmr.2023.12931
MLA
Zhao, J., Ma, M., Li, L., Fang, G."Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis". Molecular Medicine Reports 27.2 (2023): 44.
Chicago
Zhao, J., Ma, M., Li, L., Fang, G."Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK‑mediated ferroptosis". Molecular Medicine Reports 27, no. 2 (2023): 44. https://doi.org/10.3892/mmr.2023.12931
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